Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis

Jiao, Delong; Cai, Zhenyu; Choksi, Swati; Ma, Dan; Choe, Mu Hyeon; Kwon, Hyeok‐Jung; Baik, Jin Young; Rowan, Brian G.; Chen, Xiaofei; Liu, Zheng-gang

doi:10.1038/s41422-018-0058-y

Cited by 144 publications

(131 citation statements)

References 12 publications

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…As shown in our publication, we found that MLKL phosphorylation happens in dying cells in tumor necrotic areas and demonstrated that necroptosis is indeed engaged during tumor necrosis [41]. More importantly, tumor necrosis is largely suppressed upon necroptosis blockage by the deletion of MLKL gene and interestingly, the remaining tumor death in MLKL-null tumors is apoptotic [41]. These findings suggest that necroptosis of tumor cells is most likely the major cause of tumor necrosis and provides a feasible tool to assess the role of tumor necrosis in tumorigenesis [41].…”

Section: Necroptosis Of Tumor Cells and Tumor Necro-sissupporting

confidence: 75%

“…To explore the possible molecular mechanism of tumor necrosis, we recently tested if the necroptotic pathway is involved in tumor necrosis. As shown in our publication, we found that MLKL phosphorylation happens in dying cells in tumor necrotic areas and demonstrated that necroptosis is indeed engaged during tumor necrosis [41]. More importantly, tumor necrosis is largely suppressed upon necroptosis blockage by the deletion of MLKL gene and interestingly, the remaining tumor death in MLKL-null tumors is apoptotic [41].…”

Section: Necroptosis Of Tumor Cells and Tumor Necro-sissupporting

confidence: 68%

“…Although this study demonstrated the promoting effect of RIPK1 and RIPK3 in tumor development, necroptosis of tumor cells during tumor progression was not investigated. Most recently, we found that necrop-tosis happens in tumor necrotic areas and that blocking necroptosis switches tumor necrosis to tumor apoptosis [41]. Importantly, as necroptosis only happens in the late stage of tumor development in the breast cancer model used in our study, we found that inhibition of necroptosis reduces the late stage tumor growth and has no effect on tumor initiation and early growth [41].…”

Section: Necroptosis In Tumorigenesis a Dual Role In Cancer Development?supporting

confidence: 56%

“…More importantly, tumor necrosis is largely suppressed upon necroptosis blockage by the deletion of MLKL gene and interestingly, the remaining tumor death in MLKL-null tumors is apoptotic [41]. These findings suggest that necroptosis of tumor cells is most likely the major cause of tumor necrosis and provides a feasible tool to assess the role of tumor necrosis in tumorigenesis [41].…”

Section: Necroptosis Of Tumor Cells and Tumor Necro-sismentioning

confidence: 95%

See 3 more Smart Citations

Necroptosis, tumor necrosis and tumorigenesis

Liu

Jiao

2020

CST

Self Cite

130

View full text Add to dashboard Cite

Necroptosis, known as programmed necrosis, is a form of caspase-independent, finely regulated cell death with necrotic morphology. Tumor necrosis, foci of necrotic cell death, occurs in advanced solid tumors and is often associated with poor prognosis of cancer patients. While it is well documented that apoptosis plays a key role in tumor regression and the inactivation of apoptosis is pivotal to tumor development, the role of necroptosis in tumorigenesis is still not fully understood as recent studies have reported both tumor-promoting and tumor-suppressing effects of necroptosis. In this short review, we will discuss some recent studies about the role of necroptosis in tumorigenesis and speculate the implications of these findings in future research and potential novel cancer therapy targeting necroptosis.

show abstract

Section: Necroptosis Of Tumor Cells and Tumor Necro-sissupporting

confidence: 75%

Section: Necroptosis Of Tumor Cells and Tumor Necro-sissupporting

confidence: 68%

Section: Necroptosis In Tumorigenesis a Dual Role In Cancer Development?supporting

confidence: 56%

Section: Necroptosis Of Tumor Cells and Tumor Necro-sismentioning

confidence: 95%

See 2 more Smart Citations

Necroptosis, tumor necrosis and tumorigenesis

Liu

Jiao

2020

CST

Self Cite

130

View full text Add to dashboard Cite

show abstract

“…Indeed, the initiation of necroptosis can prevent tumor development in cells where apoptosis failed. However, at the same time, as a necrotic CD modality, the inflammatory response that is created after the release of DAMPs promotes angiogenesis, cell proliferation, and metastasis [6,[27][28][29][30][31] (Table 1). Table 1.…”

Section: Figurementioning

confidence: 99%

Necroptosis in Cholangiocarcinoma

Sarcognato

Jong

Fabris

et al. 2020

Cells

View full text Add to dashboard Cite

Necroptosis is a type of regulated cell death that is increasingly being recognized as a relevant pathway in different pathological conditions. Necroptosis can occur in response to multiple stimuli, is triggered by the activation of death receptors, and is regulated by receptor-interacting protein kinases 1 and 3 and mixed-lineage kinase domain-like, which form a regulatory complex called the necrosome. Accumulating evidence suggests that necroptosis plays a complex role in cancer, which is likely context-dependent and can vary among different types of neoplasms. Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis and, as a pro-inflammatory death type, it may inhibit tumor progression by releasing damage-associated molecular patterns to elicit robust cross-priming of anti-tumor CD8+ T cells. The development of therapeutic strategies triggering necroptosis shows great potential for anti-cancer therapy. In this review, we summarize the current knowledge on necroptosis and its role in liver biliary neoplasms, underlying the potential of targeting necroptosis components for cancer treatment.Cells 2020, 9, 982 2 of 18 (RIPK3) and mixed lineage kinase domain-like (MLKL) [4]. Therefore, necroptosis is an alternative mode of CD when the caspase-8-dependent apoptotic pathway is blocked. It is now well-established that various stimuli can initiate necroptosis, including intra-and extracellular factors, such as tumor necrosis factor α (TNFα) and reactive oxygen species (ROS) [5].A hallmark of cancer is the ability of malignant cells to evade apoptosis. Therefore, the induction of necroptosis could be an alternative strategy for killing cancer cells. Several therapeutics able to affect the necroptotic cascade have recently been developed, and a few of them are already in phase 1 trials for the treatment of inflammatory diseases. Moreover, necroptosis modulation is becoming the target of several new anti-cancer strategies. In fact, it has been demonstrated that apoptosis-resistant tumors respond to necroptosis, and that necroptosis can create an immunogenic microenvironment that enhances tumor clearance [6]. These aspects will be further discussed in the following chapters.Herein, we will discuss the general aspects of necroptosis and what is currently known on its involvement in cholangiocarcinoma (CCA), in order to provide perspectives for future studies in this relatively new field. Overview on Types of Cell DeathIn 2005, the Nomenclature Committee on Cell Death (NCCD) defined the first CD classification purely based on morphological criteria. This classification included three major forms of CD: types I, II, and III [7]. Type I CD, termed apoptosis, exhibits cell shrinkage, membrane blebbing, DNA fragmentation, chromatin condensation, and the formation of apoptotic bodies. Apoptosis is a form of RCD and responds to two different death signals: damage from inside the cell, such as DNA damage, which elicits an intrinsic pathway, and extracellular stimuli, such as TNFα and the Fas ligand, ...

show abstract

Linear ubiquitination‐induced necrotic tumor remodeling elicits immune evasion

et al. 2023

View full text Add to dashboard Cite

Tumor‐elicited inflammation confers tumorigenic properties, including cell death resistance, proliferation, or immune evasion. To focus on inflammatory signaling in tumors, we investigated linear ubiquitination, which enhances the nuclear factor‐κB signaling pathway and prevents extrinsic programmed cell death under inflammatory environments. Here, we showed that linear ubiquitination was augmented especially in tumor cells around a necrotic core. Linear ubiquitination allowed melanomas to tolerate the hostile tumor microenvironment and to extend a necrosis‐containing morphology. Loss of linear ubiquitination resulted in few necrotic lesions and growth regression, further leading to repression of innate anti‐PD‐1 therapy resistance signatures in melanoma as well as activation of interferon responses and antigen presentation that promote immune‐mediated tumor eradication. Collectively, linear ubiquitination promotes tumor‐specific tissue remodeling and the ensuing immune evasion.

show abstract

Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis

Cited by 144 publications

References 12 publications

Necroptosis, tumor necrosis and tumorigenesis

Necroptosis, tumor necrosis and tumorigenesis

Necroptosis in Cholangiocarcinoma

Linear ubiquitination‐induced necrotic tumor remodeling elicits immune evasion

Contact Info

Product

Resources

About